A Phase 2 clinical trial evaluating the safety and efficacy of delandistrogene moxeparvovec (SRP-9001) in patients with Duchenne muscular dystrophy

Topic:

Clinical Trials

Poster Number: 50

Author(s):

Jerry Mendell, MD, Nationwide Children’s Hospital, Perry Shieh, MD, University of California, Los Angeles, David Geffen School of Medicine, Zarife Sahenk, Center for Gene Therapy, Nationwide Children’s Hospital; The Ohio State University, Kelly J Lehman, APN, Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital, Linda Lowes, PhD, Abigail Wexner Research Institute at Nationwide Children's Hospital, Natalie Reash, DPT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Megan Iammarino, DPT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Lindsay Alfano, DPT, PCS, Abigail Wexner Research Institute at Nationwide Children's Hospital, Brenna Powers, Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital, Jeremy D Woods, UCLA Medical Center, Christy L Skura, UCLA Medical Center, Howard C Mao, UCLA Medical Center, Loretta A Staudt, PT, MS,UCLA Medical Center, Rachael A Potter, Center for Gene Therapy, Nationwide Children’s Hospital; Sarepta Therapeutics, Inc, Danielle Griffin,Sarepta Therapeutics, Inc., Sarah Lewis, Sarepta Therapeutics, Inc., Larry Hu, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Sameer Upadhyay, Sarepta Therapeutics, Inc, Teji Singh, MD, Sarepta Therapeutics, Louise R Rodino-Klapac, PhD, Sarepta Therapeutics, Inc.

Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy developed for targeted skeletal and cardiac muscle expression of micro-dystrophin, a shortened, functional, dystrophin protein.

Objective: This three-part, Phase 2 clinical trial (NCT03769116) evaluates the safety and efficacy of systemic gene transfer of delandistrogene moxeparvovec in patients with Duchenne muscular dystrophy (DMD).

Results: Part 1 is a 48-week, randomized, double-blind, placebo-controlled period. Part 2 is a 48-week period in which patients, randomized to placebo in Part 1, receive delandistrogene moxeparvovec. Part 3 is an open-label, follow-up period (?212 weeks).
Participants from Part 1 (N=41) were 4–7-year-old ambulatory boys with confirmed DMD mutation between exons 18–58 and stable steroid dosing. The intended dose was 2.0×1014 vg/kg (supercoiled qPCR, linear plasmid standard equivalent of 1.33×1014 vg/kg).

Randomization was stratified by age (4–5 and 6–7 years). Primary endpoints were change from baseline in micro-dystrophin expression (western blot; baseline to Week 12) and North Star Ambulatory Assessment (baseline to Week 48). Safety endpoints included serious adverse events and treatment-emergent adverse events.

One-year functional results from Part 1 have been presented previously. Full analyses from Parts 1 and 2 will be presented, including 2-year functional and safety data from patients who received delandistrogene moxeparvovec in Part 1; 1-year functional and safety data from patients who received delandistrogene moxeparvovec in Part 2; and expression data for all patients 12 weeks post-delandistrogene moxeparvovec infusion and 60 weeks post-infusion for those dosed in Part 1.

Conclusions: Results suggest that delandistrogene moxeparvovec has a biological effect that may be clinically relevant in people with DMD. Results reinforce a potentially favorable benefit-risk profile.

This study is funded by Sarepta Therapeutics, Inc.